Both in individuals living with cancer and in the general population, the experience of clinical depression exacts a profound psychological, physical, and economic toll. Little research has examined the unfolding risk for depressive symptoms and episodes after a breast cancer diagnosis with careful assessments repeated over time. Moreover, theory and research in depression and in emotion science have not been integrated and tested in sophisticated biopsychosocial models to advance understanding of risk and protective factors/processes for depression in cancer patients. Accordingly, this study has three specific aims. Aim 1 is to investigate how personal vulnerabilities, cancer-related (e.g., treatments/side effects) and noncancer-related stressors, and emotion regulation processes shape trajectories of depression in women following diagnosis of breast cancer. Personal vulnerabilities include general depressive diatheses (history of depression, neuroticism, harsh early environment) and emotion dysregulation diatheses (low emotional awareness and acceptance, high emotional suppression, no intimate confiding relationship). Aim 2 is to examine a diathesis- stress model, in which interactions of personal vulnerabilities, genetic factors (a functional polymorphism of the serotonin transporter gene), and stressors shape depressive response. Aim 3 is to examine a proximal model of how emotion regulation processes (approach and avoidance) mediate the effects of personal vulnerabilities on depressive symptoms and episodes. We will accomplish these aims in longitudinal research beginning within three months of diagnosis (Time 1) of 450 women (study completers) with new diagnoses of initial or recurrent invasive breast cancer and subsequent assessments every six weeks through six months (Time 2-5) and at 9 months (Time 6) and 12 months (Time 7). DNA extraction, validated questionnaires and interviews, and measures of expressive behavior will be administered. Primary dependent variables are depressive symptoms and depressive disorder. Effects of age, ethnicity, and mental health treatment receipt will be explored. Findings will influence public health by informing the next generation of targeted preventive and therapeutic interventions for depression in cancer patients, thereby reducing the disorder's health and economic burden.